Hereditary Colorectal Cancer (CRC) Program in Latvia

Irmejs Arvids, Gardovskis Andris, Borosenko Viktors, Bitina Marianna, Aigare Diana, Kurzawski Grzegorz, Suchy Janina, Górski Bohdan, Gardovskis, Gardovskis Janis

Description

The aim of the study is to evaluate the incidence and phenotype - genotype characteristics of hereditary colorectal cancer syndromes in Latvia in order to develop the basis of clinical management for patients and their relatives affected by these syndromes. Materials and methods From 02/1999-09/2002 in several hospitals in Latvia cancer family histories were collected from 865 patients with CRC. In families suspected of having a history consistent with a hereditary colorectal cancer syndrome, DNA testing for MLH1, MSH2 and MSH6 genes was performed. In addition immunohistochemical (IH) examination of the normal and cancer tissue from large bowel tumors for MSH2 and MSH6 protein expression was performed prior to DNA analysis. Results From the 865 CRC cases only 3 (0.35%) pedigrees fulfilled the Amsterdam II criteria of Hereditary Nonpolyposis Colorectal Cancer (HNPCC) and 15 cases (1.73%) were suspected of HNPCC. In 69 cases (8%) with a cancer family aggregation (CFA) were identified. Thus far 27 IH analyses have been performed and in 3 cancers homogenous lack of MSH2 or MSH6 protein expression was found. In one of these cases a mutation in MSH6 was identified. In 18 patients suspected of HNPCC or of matching the Amsterdam II criteria, denaturing high performance liquid chromatography (DHPLC) followed by DNA sequencing of any heteroduplexes of the 35 exons comprising both MLH1 and MSH2 was performed revealing 3 mutations. For all of kindreds diagnosed definitively or with a high probability of being an HNPCC family appropriate recommendations concerning prophylactic measures, surveillance and treatment were provided in written form. Conclusions Existing pedigree/clinical data suggest that in Latvia the frequency of HNPCC is around 2% of consecutive colorectal cancer patients. It is crucial that genetic counseling is an integral part of cancer family syndrome management.

Sujets

• Heredity
• Colorectal cancer

Informations

• Publié par: biomed
• Publié le: 01 janvier 2003
• Nombre de lectures: 16
• Langue: English

Extrait

Hereditary Cancer in Clinical Practice 2003; 1(1) pp. 49-53

Hereditary Colorectal Cancer (CRC) Program in Latvia

1 1 1 1 1 Arvids Irmejs , Andris Gardovskis , Viktors Borosenko , Marianna Bitina , Diana Aigare , 2 2 2 1 Grzegorz Kurzawski , Janina Suchy , Bohdan Górski , Janis Gardovskis

1 2 Hereditary Cancer Institute, Riga Stradins University, Riga, Latvia; International Hereditary Cancer Center, Pomeranian Medical University, Szczecin Poland

Key words: hereditary, colorectal cancer

Corresponding author: Arvids Irmejs, Hereditary Cancer Institute of Riga Stradins University, Dzirciema str. 16, LV 1007, Riga, Latvia. Phone: [phone]; fax: [phone]; e -mail: [e-mail]

Abstract

Introduction. The aim of the study is to evaluate the incidence and phenotype - genotype characteristics of hereditary colorectal cancer syndromes in Latvia in order to develop the basis of clinical management for patients and their relatives affected by these syndromes. Materialandmethods. From 02/1999-09/2002 in several hospitals in Latvia cancer family histories were collected from 865 patients with CRC. In families suspected of having a history consistent with a hereditary colorectal cancer syndrome, DNA testing for MLH1, MSH2 and MSH6 genes was performed. In addition immunohistochemical (IH) examination of the normal and cancer tissue from large bowel tumors for MSH2 and MSH6 protein expression was performed prior to DNA analysis. Results. From the 865 CRC cases only 3 (0.35%) pedigrees fulfilled the Amsterdam II criteria of Hereditary Nonpolyposis Colorectal Cancer (HNPCC) and 15 cases (1.73%) were suspected of HNPCC. In 69 cases (8%) with a cancer family aggregation (CFA) were identified. Thus far 27 IH analyses have been performed and in 3 cancers homogenous lack of MSH2 or MSH6 protein expression was found. In one of these cases a mutation in MSH6 was identified. In 18 patients suspected of HNPCC or of matching the Amsterdam II criteria, denaturing high performance liquid chromatography (DHPLC) followed by DNA sequencing of any heteroduplexes of the 35 exons comprising both MLH1 and MSH2 was performed revealing 3 mutations. For all of kindreds diagnosed definitively or with a high probability of being an HNPCC family appropriate recommendations concerning prophylactic measures, surveillance and treatment were provided in written form. Conclusions. Existing pedigree/clinical data suggest that in Latvia the frequency of HNPCC is around 2% of consecutive colorectal cancer patients. It is crucial that genetic counseling is an integral part of cancer family syndrome management.

Introduction

During the last decade dramatic changes have taken place in the diagnosis and management of familial/hereditary colorectal cancer syndromes. New developments are offering possibilities of early cancer detection, improvements in treatment and preventive measures for the affected and persons at risk of disease. Hereditary cancer management has developed as an essential part of modern oncology treatment and current practice reveals the importance of cancer genetic services in providing the best care for hereditary cancer syndrome patients.

HereditaryCancerinClinicalPractice 2003; 1(1)

Latvia is an East European country located in the Baltic region with approximately 2.4 million of inhabitants. In the year 2002 there were 8977 new cancer cases detected in Latvia, including 926 colorectal cancer cases. From all newly diagnosed cancers only 17.4% were detected in stage I, and 22.9% in stage of the II disease. According to epidemiological data available for familial colorectal cancer, one would expect somewhere in between 90 and 130 familial cases in Latvia annually. From this estimate, 20-60 of them are most likely to be associated with hereditary condition (either HNPCC or FAP). Detection and appropriate management of patients affected with disease or those

49